Neural Control of Movement This project is devoted to understanding the nature of neuronal and muscular mechanisms required for clear vision and attention and perception. Our interest in normal behavior is motivated by clinical disorders, such as misalignment of the two eyes (strabismus), oscillations of the eyes (e.g., tremor, flutter and opsoclonus), and difficulty with visual perception. Recent studies have shown that systems for vision and action interact, and thus a fuller understanding of our visual system requires study of both motor and sensory systems. We are looking into the network of areas that are involved in action and perception to understand how they may be coupled. One area that is important for making decisions about which target to select is the basal ganglia, and another is the cerebellum. We are studying patients with cerebellar deficits (e.g., spinal cerebellar ataxia) and basal ganglia deficits (e.g., Parkinson's disease). This should give us a clearer understanding of how these important brain areas cooperate to select the goal of an eye movement. Attention and Perception An important aspect of vision is that it takes time to perceive a new object. When the new object appears in a peripheral location it is common for an eye movement to bring the image of the object onto the fovea (the area of highest visual acuity). It seems obvious that perception and action should be tightly coupled in time. There is no point in looking at an object you can't perceive, and vice versa. Nonetheless, the pathways for vision and action are different, and whether or how they may be coupled remains unknown. We have been studying the saccadic reaction time, the perceptual reaction time, and what is perceived by human subjects. Surprisingly, we find that all three share a common time course, suggesting that they may be sharing the same trigger for their response. Evidence suggests that an area in the midbrain, called the superior colliculus, may be key for coupling action and perception. Stereo Vision Each of our two eyes sees a slightly different view of the world. This allows us to perceive depth and disparity. We study these phenomena by using the ultra-short latency ocular following response. This is a machine-like, low-level response of the visual system to motion across the retina. With it, we can study both response to moving images, and response to image depth and disparity. We have also shown that, with appropriate visual stimulation, different movements are produced in normal and stereoblind subjects, indicating that these movements might have diagnostic value. Clinical Eye Movement Disorders We have looked at several clinical disorders of eye movements. We found that motor learning in cerebellar disease may be linked to disordered activity in the inferior olive, which provides an important input to the cerebellum. We also looked at patients with cerebrotendinous xanthomatosis, a metabolic disorder that affects the dentate nuclei of the cerebellum. Deficits in these patients allowed us to show, for the first time, that the dentate nuclei are involved in controlling the precision, as opposed to the accuracy, of movements. Careful analysis of a subject with opsoclonus (wild, multi-axis gyrations of the eyes), allowed us to propose the first model of a wide variety of eye movements seen in opsoclonus patients. The inference from our patient was that opsoclonus could be caused by an up-regulation of GABAA receptor function in an olivary-cerebellar-brainstem network.